CICS, Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal.
AAPS PharmSciTech. 2010 Mar;11(1):233-40. doi: 10.1208/s12249-009-9375-2. Epub 2010 Feb 5.
In this study, we investigate how the effect of L-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the apparent stability constants (K(1:1)) of the inclusion complexes formed between OME and each cyclodextrin, beta-cyclodextrin (betaCD), and methyl-beta-cyclodextrin (MbetaCD) is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect is more pronounced for the OME:betaCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution. The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations.
在这项研究中，我们研究了 L-精氨酸（ARG）和环糊精对奥美拉唑（OME）稳定性和溶解度的影响。通过相溶解度图和核磁共振（NMR）光谱研究了 ARG 存在对 OME 与每个环糊精（β-环糊精（βCD）和甲基-β-环糊精（MbetaCD））形成的包合物的表观稳定常数（K（1：1））的影响。使用 NMR 光谱和分子动力学模拟表征了 ARG 存在时 OME 与这些环糊精的相互作用。与不存在时形成的包合物相比，ARG 显著增加了药物的溶解度和络合物稳定性。对于 OME：βCD 络合物，效果更为明显。ARG 也有助于提高游离水溶液中 OME 的稳定性。ARG 与环糊精的结合可以成为开发稳定药物制剂的重要工具。
